Ketamine suppresses hypoxia‐induced inflammatory responses in the late‐gestation ovine fetal kidney cortex

Chang, Eileen I.; Zarate, Miguel; Rabaglino, María Belén; Richards, Elaine M.; Keller‐Wood, Maureen; Wood, Charles E.

doi:10.1113/jp271066

Cited by 25 publications

(33 citation statements)

References 61 publications

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“…We find it interesting and intriguing that the increase in macrophages/microglia in the fetal cerebral cortex appears to be very similar to an increase in macrophages in the renal cortex of the fetus, recently reported elsewhere (Chang et al. ).…”

Section: Discussionsupporting

confidence: 89%

Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex

et al. 2016

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Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti‐inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30‐min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3–5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.

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Section: Discussionsupporting

confidence: 89%

Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex

et al. 2016

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“…Moreover, ketamine has been found to inhibit the inflammatory response in the fetal cerebral cortex, which undergoes transient hypoxia . In addition, ketamine can also reduce hypoxia‐mediated inflammation and apoptosis in fetal ovine kidneys . In line with these data, we and other investigators have also demonstrated that ketamine is effective in the prevention of LPS‐mediated microglial inflammation .…”

Section: Discussionsupporting

confidence: 82%

Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

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et al. 2019

Fundamemntal Clinical Pharma

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Microglial inflammation leads to the upregulation of proinflammatory cytokine and proinflammatory enzyme expression, resulting in inflammation‐induced neuronal cell apoptosis. Ketamine, an anesthetic mostly used in critical patients, has been reported to possess neuroprotective effects. However, the potential mechanism is still not well understood. In the present study, we investigated how ketamine attenuates lipopolysaccharide (LPS)‐mediated BV2 cell inflammation. LPS upregulated proinflammatory cytokine and proinflammatory enzyme expression, increased NF‐κB phosphorylation and nuclear translocation, and augmented calcium (Ca2+)/calmodulin‐dependent protein kinase II (CaMK II) phosphorylation and Ca2+ levels in BV2 cells. Ketamine could reverse these LPS‐induced effects. Furthermore, AP5, an inhibitor of NMDA receptors, inhibited LPS‐induced inflammatory effects in BV2 cells, which was similar to the effects of ketamine. Moreover, these effects of ketamine against LPS‐mediated inflammation in BV2 cells could be reversed by D‐serine, an activator of NMDA receptors. The present study suggests that ketamine, by inhibiting NMDA receptors, attenuating Ca2+ levels, and inhibiting CaMK II phosphorylation, NF‐κB phosphorylation and nuclear translocation, may ameliorate LPS‐mediated inflammation in BV2 cells.

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“…In a recent study, researchers intravenously administered ketamine into fetal sheep before inducing hypoxia. Ketamine ameliorated the upregulation of inflammatory pathways and reduction of metabolism caused by hypoxia [45]. Furthermore, thiopental pretreatment reduced renal IR injury induced by free radicals [46, 47].…”

Section: General Anesthesiamentioning

confidence: 99%

A Review of Anesthetic Effects on Renal Function: Potential Organ Protection

et al. 2017

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Background: Renal protection is a critical concept for anesthesiologists, nephrologists, and urologists, since anesthesia and renal function are highly interconnected and can potentially interfere with one another. Therefore, a comprehensive understanding of anesthetic drugs and their effects on renal function remains fundamental to the success of renal surgeries, especially transplant procedures. Some experimental studies have shown that some anesthetics provide protection against renal ischemia/reperfusion (IR) injury, but there is limited clinical evidence. Summary: The effects of anesthetic drugs on renal failure are particularly important in the context of kidney transplantation, since the conditions of preservation following removal profoundly influence the recovery of organ function. Currently, preservation procedures are typically based on the usage of a cold-storage solution. Some anesthetic drugs induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. A more thorough understanding of anesthetic effects on renal function can present a novel approach for developing organ-protective strategies. The aim of this review is to discuss the effects of different anesthetic drugs on renal function, with particular focus on IR injury. Many studies have demonstrated the organ-protective effects of some anesthetic drugs, specifically propofol, which indicate the potential of some anesthetics to introduce novel organ protective targets. This is not surprising, since lipid emulsions are major components of propofol, which accumulating data show provide organ protective effects against IR injury. Key Messages: Thorough understanding of the interaction between anesthetic drugs and renal function remains fundamental to the delivery of safe perioperative care and to optimizing outcomes after renal surgeries, particularly transplant procedures. Anesthetics can be repurposed for organ protection with more information about their effects, especially during transplant procedures. Here, we review the effects of different anesthetic drugs – specifically those that contain lipids in their structure, with special reference to IR injury.

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Ketamine suppresses hypoxia‐induced inflammatory responses in the late‐gestation ovine fetal kidney cortex

Cited by 25 publications

References 61 publications

Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex

Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex

Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

A Review of Anesthetic Effects on Renal Function: Potential Organ Protection

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